Connective Tissue Physiology (10/21a) [Biomedical] Flashcards
Tendon
parallel fibers, muscle to bone
Ligament
mostly parallel fibers, bone to bone
Tendon/Ligament Components
MAIN
- cells
- collagen fibers (types 1 and 3)
OTHERS
- water
- elastin
- proteoglycans/GAGs
- minor collagens
Proteoglycan/GAG function
negatively charged
attract water
help lubricate tissues
Viscoelastic Properties - Creep
application of constant load within elastic limit
transient change
Viscoelastic Properties - Stress Relaxation
application of constant deformation and over time the load becomes perceived as less stressful
Viscoelastic Properties - Cyclic Loading
when you load the tissue for repeated cycles, a few reps in is more reproducible than the first rep
Sprain vs Strain
Sprain — ligament or capsule
Strain — muscle or tendon
Sprain Grades
Grades 1 and 2 experience microtrauma, pain, some swelling
Grade 3 experiences macrotrauma, least stable, swelling, some pain
Microtrauma
small tears in CT and fibers that cause damage over time, caused by repetitive stress
Macrotrauma
caused by a traumatic event or forceful blow
Study of Injury Grades in Animals
We have tested tensile properties in animal models
Ultimate stress is greatly reduced in healing transected (macrotrauma) ligaments
Threshold for Injury
Consider Physical Stress Theory
For certain injuries, may have lower set points for thresholds
May have severely limited ultimate stress points
Three Phases of Tissue Healing
Acute Inflammation (0-5 days) — necessary to start healing process
Repair (3-28 days) — fibroblasts secrete collagen
Maturation/Remodeling (3 days-1 year) — improving the tensile strength of collagen
Tissue Healing - Acute Inflammation, Overview
(0-5 days)
Injury and Brief Vasoconstriction
Arterial Vasodilation
- edema formation
Clot Formation
- Prothrombin → Thrombin → Fibrin → Scar Tissue
Cellular Infiltration
Cytokine Production
Tissue Healing - Acute Inflammation, Treatment
Treat to control from spreading/worsening
POLICE
- protect against further injury/inflammation
- optimal loading to help recruit other cells
- ice to vasoconstrict and reduce secondary inflammation and also control pain
- compression and elevation to move the swelling away from the area
Tissue Healing - Repair, Overview
(3-28 days)
Growth factor expression
- produced mainly by activated macrophages & platelets (EX: IGF-1)
- function – angiogenesis, proliferation of fibroblasts, collagen synthesis, collagenase secretion
- proinflammatory cytokines — not good and can lead to negative cascade of events (EX: interleukin-1)
New vessel formation
Collagen synthesis exceeds lysis
Increased crosslinks (H+ bonding) - increasing tensile strength
Collagen Type III gradually replaced by Type I
Increased cells, GAGs, water
Tissue Healing - Repair, Treatment
wrapping
open chain low load exercise
isometrics
stability and strength in distal and proximal
Tissue Healing - Maturation, Overview
(3 days-1 year, can be up to 2 years)
Tendons and ligaments heal through scarring
Collagen synthesis = lysis
Conversion to type I collagen completed
More mature crosslinks (covalent)
Orderly alignment of collagen
Decreasing cellularity and vascularity
Tissue Healing - Maturation, Treatment
Increasing difficulty of exercises, considering what other demands you can meet
Specific Adaptation to Imposed Demands (S.A.I.D) principle
EdUReP (Education, Unloading, Reloading, Prevention)
- EX: popular for tendinopathy
3 Mechanisms of Loading/Unloading CT
Growth Factors
Stretch Activated Pathways
ECM Integrins
CT Mechanism - Growth Factors
Growth factor receptors on the membrane and have a connection to the nucleus
Mechanically load tissue → growth factors released → bind to receptors
Signal transduction pathway activated → nucleus told to produce more collagen/fibroblasts
CT Mechanism - Stretch Activated Pathways
Activate transduction signals that tell the nucleus to produce more collagen and fibroblasts
CT Mechanism - ECM Integrins
Communicate to nucleus via integrins (proteins that are on cell membrane)
Tell nucleus to produce more collagen and fibroblasts
Normal CT - Response to Loading
Consistent, prolonged exercise
Initiates a low‐level inflammatory response (acutely)
Upregulates collagenase synthesis (acutely)
Upregulates type I collagen synthesis (acutely & chronic)
- increased net type I collagen synthesis
Normal CT - Response to Immobilization
Decreased collagen biosynthesis
- decreased enzyme activities
- decreased mRNA for type I & III collagen
- appears to be stretch sensitive
Increased collagen degradation
- increased expression of matrix metalloproteinases (MMPs)
Why don’t you want an over expression of matrix metalloproteinases (MMPs)?
you will get more collagen breakdown than you want
Type 1 vs Type 3 Collagen
type 1 gives tensile strength (enzymatic crosslinks)
type 3 gives flexibility
Healing CT - Response to Immobilization
BIOCHEMICAL
- decreased collagen (decreased collagen synthesis, increased collagen lysis)
- increased weak crosslinks
- decreased GAG, HA, water content
MORPHOLOGIC
- adhesions, contractures, less orderly collagen fibers
BIOMECHANICAL
- decreased tissue stiffness
- decreased load to failure
Examples of Healing CT’s response to immoblization
EX: decreased elastic modulus (stiffness)
- decreased stiffness 6 weeks after repair
- increased stiffness during cyclic loading
EX: increased creep
- deformation is much higher in scar tissue than normal tissue
EX: differences in collagen
- compared to normal ligament collagen, scar collagen is smaller, more uniform shape and size, but there are scar defects
Healing CT - Response to Remobilization
BIOCHEMICAL
- mechanical loading induces secretion of growth factors
- increase collagen synthesis, ECM protein ‐ PGs
MORPHOLOGIC
- in ambulatory rats, you see more cells at 3 weeks
- in unloaded rats, you still see cells but not really in parallel structure
BIOMECHANICAL
- people cannot withstand the same force they did before the injury
- stiffness is highly decreased
